PROJECT SUMMARY/ABSTRACT Opioids are commonly prescribed to patients on dialysis for pain or the treatment of opioid use disorder; however, practitioners lack basic outcome data on the safety of these medications in end-stage renal disease patients where the risk of sudden cardiac arrest is 30 times higher than the population average. For example, both methadone and oxycodone have been implicated in the prolongation of the QTc interval, which can precipitate fatal arrhythmias such as torsade de pointes. Similarly, propoxyphene has type 1A antidysrhythmic properties with QRS prolongation and potential fatal arrhythmias. Taken all together, the interaction between a proarrhythmic drug and patients with high cardiovascular burden may unknowingly place dialysis patients at excess risk for sudden cardiac arrest. We have preliminary data suggesting that patients seeking methadone therapy from a licensed opioid treatment program are more than twice as likely to die from sudden cardiac arrest when compared patients receiving buprenorphine for opioid use disorder. The intent of this proposal is to investigate the cardiovascular safety between opioid drug classes in a larger dataset through the linkage of external claims with substance abuse data to 15 years of electronic health record data. We will compare the rate of sudden cardiac arrest by drug class in dialysis patients receiving opioids for pain control or opioid use disorder. We believe this exploratory R21 mechanism will permit a collaborative team of addiction, renal, and biostatical investigators to address an important gap in clinical knowledge for physicians who care for patients with ESRD. This proposal has the potential to lead to changes in the practice of pain management and opioid use disorder in patients on dialysis.